Macrophages are key cells that direct innate immune responses to pathogens that are detected throughspecific pattern recognition receptors. We will analyze the transcriptomes of macrophages infected withBurkholderia pseudomallei and determine the transcription factors and signaling molecules that are activatedin response to infection. By examining macrophages deficient for central signaling molecules, we willascribe specific transcriptional clusters to TLR signaling (MyD88/Trif null cells), NLR signaling (Rip2 orcaspase 1 null cells) or type I interferon signaling (IFNaRI null cells). In parallel, we will determine thetranscriptional response to specific bacterial virulence factors or PAMPs in B. pseudomallei, including thetype III and VI secretion systems, actin polymerization, flagellin and quorum sensing. We willcomputationally identify specific transcription factors that are activated and identify the compendium of genesthat each of three transcription factor regulates. Finally, we will validate the transcriptional networks that aredefined and determine their effect on B. pseudomallei infection in vivo and in vitro.
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